In vitro investigation into the relationship of prolactin/prolactin receptor with ochratoxin a toxicity in rat liver cell line

Ochratoxin A (OTA) is a fungal toxin and many foods are contaminated by OTA. OTA damages multiple tissues, especially the kidney and liver, and is classified as a possible human carcinogen. One of the damaging mechanisms of OTA is its disruption of the regulation of cellular signaling pathways, and this study aimed to investigate the relationship of prolactin receptor forms with this mechanism. It was found that the lowest dose of OTA that significantly reduced the viability of the WB-F344 rat liver cell line at 24 hours was 10 μM. Therefore, the WB-F344 cell line was exposed to 10 μM OTA for up to 24 hours and the levels of prolactin receptor signaling-related proteins were examined by Western blot method. Exposure to OTA for 24 hours reduced short form prolactin receptor protein level in WB-F344 cell line. Additionally, it was observed that the phosphorylation level of ERK and AKT, which are also downstream targets of prolactin receptor signaling, increased in a time-dependent manner with 10 μM OTA exposure. It is thought that the reason for the change in short form prolactin receptor expression may be miRNAs whose expression changes depending on OTA. A phosphatase (DUPD1) that carries out ERK dephosphorylation as a result of activation of the short form prolactin receptor has been described in the literature. The decrease in short-form prolactin receptor expression due to OTA exposure may result in the loss of activity of this phosphatase and contribute to the sustained phosphorylation of ERK.